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目的:探讨可溶性Jagged-1/Fc嵌合蛋白(Jagged-1)对重组小鼠粒细胞-巨噬细胞集落刺激因子(rmGM-CSF)和白细胞介素4(rmIL-4)体外诱导小鼠骨髓来源树突状细胞(DC)产生细胞因子的影响。方法:建立rmGM-CSF和rmIL-4体外诱导DC的模型,观察Jagged-1/Fc对DC分化的形态学影响,通过Luminex蛋白液相芯片技术和ELISA检测其细胞因子的表达水平,藉MTT法测定可溶性Jagged-1/Fc诱导的DC对同种异基因淋巴细胞增殖的刺激能力。结果:除了TGF-β,Jag-ged-1/Fc诱导的DC与细菌脂多糖(LPS)或酵母聚糖A诱导的DC不同,表现为生成TNF-α的水平明显降低,IL-4显著增高,而IL-10、IL-6、IL-2、IL-12和IFN-γ的水平与对照组无明显差异。γ分泌酶抑制剂DAPT能逆转Jagged-1/Fc抑制DC生成TNF-α。混合淋巴细胞反应显示Jagged-1/Fc诱导的DC对T细胞增殖的刺激能力最弱,LPS诱导的DC的刺激能力最强。结论:Jagged-1/Fc诱导的DC倾向介导免疫耐受,指导初始T细胞向Th2细胞偏离。
AIM: To investigate the effect of Jagged-1 chimeric protein (Jagged-1) on the induction of murine bone marrow in vitro by recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF) and interleukin-4 Effects of Cytokines Produced by Dendritic Cells of Origin. Methods: The models of DC induced by rmGM-CSF and rmIL-4 were established in vitro. Morphological changes of DCs induced by Jagged-1 / Fc were observed. The expression of cytokines was detected by Luminex protein chip and ELISA. Stimulation ability of soluble Jagged-1 / Fc-induced DCs on allogeneic lymphocyte proliferation was determined. RESULTS: Jag-ged-1 / Fc-induced DCs differed from those induced by bacterial lipopolysaccharide (LPS) or Zymosan A in addition to TGF-β, indicating a significant decrease in TNF-α production and a significant increase in IL-4 , While the level of IL-10, IL-6, IL-2, IL-12 and IFN-γ had no significant difference with the control group. DAPT, a γ-secretase inhibitor, reverses Jagged-1 / Fc inhibition of DC production of TNF-α. Mixed lymphocyte reaction showed that Jagged-1 / Fc-induced DCs had the weakest ability to stimulate T-cell proliferation and LPS-induced DCs had the strongest stimulation ability. CONCLUSION: Jagged-1 / Fc-induced DC tendencies mediate immune tolerance and direct the initiation of T-cell migration to Th2 cells.